Submissions for variant NM_000530.8(MPZ):c.487G>A (p.Gly163Arg) (rs281865128)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000538322	SCV000636250	pathogenic	Charcot-Marie-Tooth disease, type I	2019-12-03	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with arginine at codon 163 of the MPZ protein (p.Gly163Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Charcot-Marie-Tooth type 1 (CMT1) (PMID: 8800924) as well as in three members of a family affected with CMT1 (PMID: 27088055). ClinVar contains an entry for this variant (Variation ID: 208148). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). A different variant (c.487G>C) giving rise to the same protein effect observed here (p.Gly163Arg) has been reported to segregate with disease in two families affected with CMT1 (PMID: 12207932, 15170620), indicating that this residue may be critical for protein function. For these reasons, this variant has been classified as Pathogenic.
GeneReviews	RCV000193606	SCV000243905	pathogenic	Charcot-Marie-Tooth disease, demyelinating, type 1b	2015-03-26	no assertion criteria provided	literature only
Inherited Neuropathy Consortium	RCV000789471	SCV000928827	uncertain significance	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only

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